The use of stent medical devices to keep a duct, vessel or other body lumen open in the human body has developed into a primary therapy for lumen stenosis or obstruction. The use of stents in various surgical, interventional cardiology, and radiology procedures has quickly become accepted as experience with stent devices accumulates and as the advantages of stents become more widely recognized. Stents are often used in body lumens to maintain open passageways such as the prostatic urethra, the esophagus, the biliary tract, intestines, and various coronary arteries and veins, as well as more remote cardiovascular vessels such as the femoral artery.
Stents are often used to treat atherosclerosis, a disease in which vascular lesions or plaques consisting of cholesterol crystals, necrotic cells, lipid pools, excess fiber elements and calcium deposits accumulate in the walls of an individual's arteries. One of the most successful procedures for treating atherosclerosis is to insert a deflated balloon within the lumen, adjacent the site of the plaque or atherosclerotic lesion. The balloon is then inflated to put pressure on and “crack” the plaque. This procedure increases the cross-sectional area of the lumen of the artery. Unfortunately, the pressure exerted also traumatizes the artery, and in 30-40% of the cases, the vessel either gradually renarrows or recloses at the locus of the original stenotic lesion. This renarrowing is known as restenosis
A common approach to prevent restenosis is to deploy a stent to the site of the stenotic lesion. Stents can be made from various conventional, biocompatible metals; however, several disadvantages may be associated with the use of metal stents. For instance, although metallic stents have the mechanical strength necessary to prevent the retractile or recoil form of restenosis, their presence in the artery can lead to biological problems including vasospasm, compliance mismatch, and even occlusion. Moreover, there are inherent, significant risks from having a metal stent permanently implanted in the artery, including erosion of the vessel wall. The stents may also migrate on occasion from their initial insertion location. Such stents cause irritation to the surrounding tissues in a lumen. Also, since metals are typically much harder and stiffer than the surrounding tissues in a lumen, this may result in an anatomical or physiological compliance mismatch, thereby damaging tissue or eliciting unwanted biologic responses. In addition, the constant exposure of the stent to the blood can lead to thrombus formation within the blood vessel. Stents also allow the cellular proliferation of the injured arterial wall to migrate through the stent mesh, where the cells continue to proliferate and eventually lead to the narrowing of the vessel. Further, metal stents typically have some degree of negative recoil. Finally, metallic stents actually prevent or inhibit the natural vascular remodeling that can occur in the organism by rigidly tethering the vessel to a fixed, maximum diameter.
Similar complications and problems, as in the case of metal stents, may well result when using stents made from non-absorbable biocompatible polymer or polymer-composites, although these materials may offer certain benefits such as reduction in stiffness.
Bioabsorbable and biodegradable materials for manufacturing temporary stents present a number of advantages. The conventional bioabsorbable or bioresorbable materials of the stents are selected to absorb or degrade over time to allow for subsequent interventional procedures such as restenting of the original site if there is restenosis and insertion of a vascular graft. Further, bioabsorbable and biodegradable stents allow for vascular remodeling, which is not possible with metal stents that tethers the arterial wall to a fixed geometry. In addition to the advantages of not having to surgically remove such stents, bioabsorbable and biodegradable materials tend to have excellent biocompatibility characteristics, especially in comparison to most conventionally used biocompatible metals. Another advantage of bioabsorbable and biodegradable stents is that the mechanical properties can be designed to substantially eliminate or reduce the stiffness and hardness that is often associated with metal stents, which can contribute to the propensity of a stent to damage a vessel or lumen. Examples of novel biodegradable stents include those found in U.S. Pat. No. 5,957,975, and U.S. application Ser. No. 10/508,739, which is herein incorporated by reference in its entirety.
It is often difficult to sterilize the biodegradable polymers of the stent, however, without causing damage to the polymer itself. For instance, it is difficult to use acid to sterilize because acid can very quickly degrade the polymer and hence affect its mechanical properties. Further, it is difficult to use autoclaving to steam sterilize a biodegradable polymer. In autoclaving, sterilization condition of high-pressure vapor is applied for about 20 minutes at 121° C. of 1.0 kg/cm2G of saturated vapor pressure. While such conditions are possible in sterilization of many kinds of medical materials that stand high pressure and temperature, such sterilization methods are often problematic for organic polymer materials because of deterioration or decomposition of the material.
Many sterilizable devices that incorporate biodegradable polymers are sterilized by irradiating the device; however, there are also many problems with radiation. For instance, E-beam irradiation, particularly at doses above two Mrd, can induce significant degradation of the polymer chain, resulting in reduced molecular weight and altering the final mechanical properties and degradation time.
In addition, irradiation can cause cross-linking and collapsing of the polymer chains. Polymer cross-linking occurs because radicals are generated by the irradiation process, thereby generating new inter- and intramolecular connections of the polymer molecules. Further, the free radicals generated by irradiation do not immediately disappear, but remain in the polymer material and can cut polymer chains and lead to other problems by reacting with oxygen over time. The free radicals can generally be removed by heating the polymer to a temperature higher than 100° C.; however, this again would deform the polymer and alter its mechanical properties.
There are also differences between sterilizing metal and polymer stents by irradiation. For metal stents, the struts may be close together and even overlap during sterilization. Sterilization of biodegradable polymers by irradiation; however, may result in the struts fusing together. Further, radiation exposure may cause the polymer materials to cross-link or cause collapse of the polymer chains.
Therefore, EtO sterilization is commonly used for biodegradable polymers such as polyglycolide, poly (lactide), and poly (dioxanone). Because the highly toxic EtO can present a safety hazard; however, great care must be taken to ensure that all the gas is removed from the device before final packaging. Further, EtO sterilization occurs at elevated temperatures, and thus may again result in strut fusion.
In the case of biodegradable stents, the inventors have discovered that the stents can be sterilized by gamma irradiation when the space between the struts is large enough to prevent overlap and fusion of the struts. The inventors made the surprising discovery that carefully controlling the spacing between the struts yields superior results. This method yields stents with unexpectedly improved quality because there is minimal crosslinking and collapsing, resulting in struts that do not stick together.